Oligofluorene Antennae for Luminescent Lanthanide Cations: Synthesis and Characterization

Lanthanide complexes emit as sharp emission bands, have long luminescence lifetimes for temporal discrimination from background fluorescence and strong resistance to photobleaching. These attractive properties make lanthanide compounds potentially applicable in a variety of devices, including optical displays and sensors. However, luminescent lanthanide cations weakly absorb light, and require proximal chromophores to absorb excitation light. Energy is subsequently transferred to the lanthanide cations, resulting in the sensitization of their emission.Usually, the energy levels in a given chromophore are fixed and cannot be adjusted. In this thesis, oligofluorene ligands, comprised of either one (mono) or three (ter) fluorene units in the backbone, exhibited a tunable nature of their electronic levels directly controlled by the number of fluorene units. By varying the length of the fluorene backbone in these ligands, the donating level(s) of the chromophore was (were) discretely tuned to the accepting level(s) of a particular lanthanide (Eu and Tb). Furthermore, the lanthanide cation was coordinated to a cage-like polyaminocarboxylate moiety within the ligand, which protected the cation from non-radiative deactivation. Matching the energies of the donating electronic states of an oligofluorene ligand with the appropriate accepting levels of a lanthanide cation lead to efficient oligofluorene to lanthanide energy transfer with quantum yields of 7%, such as in the TF1:Eu3+ complex. The efficiency in these novel lanthanide complexes is comparable to established lanthanide compounds used today in fluoroimmunoassays

Development of a Molecular-Imprinted-Polymer based sensor for the electrochemical determination of Triacetone Triperoxide (TATP)

.The explosive triacetone triperoxide (TATP), which can be prepared from commercially readily available reagents following an easy synthetic procedure, is one of the most common components of improvised explosive devices (IEDs). Molecularly-imprinted polymer (MIP) electrochemical sensors have proved useful for the determination of different compounds in different matrices with the required sensitivity and selectivity. In this work, a highly sensitive and selective molecularly imprinted polymer with electrochemical capabilities for the determination of TATP has been developed. The molecular imprinting has been performed via electropolymerisation onto a glassy carbon electrode surface by cyclic voltammetry from a solution of pyrrole functional monomer, TATP template and LiClO4. Differential Pulse Voltammetry of TATP, with LiClO4 as supporting electrolyte, was performed in a potential range of −2.0 V to +1.0 V (vs. Ag/AgCl). Three-factor two-level factorial design was used to optimise the monomer concentration at 0.1 mol·L−1 , template concentration at 100 mmol·L−1 and the number of cyclic voltammetry scan cycles to 10. The molecularly imprinted polymer-modified glassy carbon electrode demonstrated good performance at low concentrations for a linear range of 82–44,300 µg·L−1 and a correlation coefficient of r2 = 0.996. The limits of detection (LoD) and quantification (LoQ) achieved were 26.9 μg·L−1 and 81.6 μg·L−1, respectively. The sensor demonstrated very good repeatability with precision values (n = 6, expressed as %RSD) of 1.098% and 0.55% for 1108 and 2216 µg·L−1 , respectively. It also proved selective for TATP in the presence of other explosive substances such as PETN, RDX, HMX, and TNT

Quality of Life after Risk-Reducing Hysterectomy for Endometrial Cancer Prevention: A Systematic Review

BACKGROUND: Risk-reducing hysterectomy (RRH) is the gold-standard prevention for endometrial cancer (EC). Knowledge of the impact on quality-of-life (QoL) is crucial for decision-making. This systematic review aims to summarise the evidence. Methods: We searched major databases until July 2022 (CRD42022347631). Given the paucity of data on RRH, we also included hysterectomy as treatment for benign disease. We used validated quality-assessment tools, and performed qualitative synthesis of QoL outcomes. RESULTS: Four studies (64 patients) reported on RRH, 25 studies (1268 patients) on hysterectomy as treatment for uterine bleeding. There was moderate risk-of-bias in many studies. Following RRH, three qualitative studies found substantially lowered cancer-worry, with no decision-regret. Oophorectomy (for ovarian cancer prevention) severely impaired menopause-specific QoL and sexual-function, particularly without hormone-replacement. Quantitative studies supported these results, finding low distress and generally high satisfaction. Hysterectomy as treatment of bleeding improved QoL, resulted in high satisfaction, and no change or improvements in sexual and urinary function, although small numbers reported worsening. CONCLUSIONS: There is very limited evidence on QoL after RRH. Whilst there are benefits, most adverse consequences arise from oophorectomy. Benign hysterectomy allows for some limited comparison; however, more research is needed for outcomes in the population of women at increased EC-risk

Breast Cancer Risk and Breast-Cancer-Specific Mortality following Risk-Reducing Salpingo-Oophorectomy in BRCA Carriers : A Systematic Review and Meta-Analysis

Funding This research was funded by Rosetrees Trust, grant number CF1\100001, and Barts Charity, grant number ECMG1C3R. The funders had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.Peer reviewedPublisher PD

Quality of life after risk-reducing surgery for breast and ovarian cancer prevention: a systematic review and meta-analysis

OBJECTIVE: To assess the impact of risk-reducing surgery (RRS) for breast cancer (BC) and ovarian cancer (OC) prevention on quality-of-life (QoL). We consider risk-reducing mastectomy (RRM), risk-reducing salpingo-oophorectomy (RRSO), and risk-reducing early-salpingectomy and delayed-oophorectomy (RRESDO). DATA SOURCES: We followed a prospective protocol (PROSPERO: CRD42022319782) and searched MEDLINE, EMBASE, PubMed, and Cochrane Library from inception to February 2023. STUDY ELIGIBILITY CRITERIA: We followed a PICOS framework. The population included women at increased risk of BC or OC. We focused on studies reporting QoL outcomes (health-related QoL (HRQoL), sexual function, menopause symptoms, body image, cancer-related distress or worry, anxiety or depression) after RRS, including RRM for BC and RRSO or RRESDO for OC. STUDY APPRAISAL AND SYNTHESIS METHODS: We used the Methodological Index for Non-Randomized Studies (MINORS) for study appraisal. Qualitative synthesis and fixed-effects meta-analysis was performed. RESULTS: Thirty-four studies were included (RRM:16 studies, RRSO: 19 studies, RRESDO: 2 studies). HRQoL was unchanged or improved in 13/15 studies post-RRM (N=986) and 10/16 studies post-RRSO (N=1617), despite short-term deficits (N=96 post-RRM and N=459 post-RRSO). Sexual function (using Sexual Activity Questionnaire) was affected in 13/16 studies (N=1400) post-RRSO, in terms of decreased sexual pleasure (-1.21[-1.53,-0.89]; N=3070) and increased sexual discomfort (1.12[0.93,1.31]; N=1400). Hormone replacement therapy after pre-menopausal RRSO was associated with an increase (1.16[0.17,2.15]; N=291) in sexual pleasure and a decrease (-1.20[-1.75,-0.65]; N=157) in sexual discomfort. Sexual function was affected in 4/13 studies (N=147) post-RRM, but stable in 9/13 studies (N=799). Body image was unaffected in 7/13 studies (N=605) post-RRM, whereas 6/13 studies (N=391) reported worsening. Increased menopause symptoms were reported in 12/13 studies (N=1759) post-RRSO with a reduction (-1.96[-2.81,-1.10]; N=1745) in Functional Assessment of Cancer Therapy-Endocrine Subscale. Cancer-related distress was unchanged or decreased in 5/5 studies post-RRM (N=365) and 8/10 studies post-RRSO (N=1223). RRESDO (2 studies, N=413) had better sexual function and menopause-specific QoL. CONCLUSION: RRS may be associated with QoL outcomes. RRM and RRSO reduce cancer-related distress, and do not affect HRQoL. Women and clinicians should be aware of body image problems post-RRM, together-with sexual dysfunction and menopause symptoms post-RRSO. RRESDO may be a promising alternative to mitigate QoL-related risks of RRSO

Superfield Description of a Self-Dual Supergravity a la MacDowell-Mansouri

Using MacDowell-Mansouri theory, in this work, we investigate a superfield description of the self-dual supergravity a la Ashtekar. We find that in order to reproduce previous results on supersymmetric Ashtekar formalism, it is necessary to properly combine the supersymmetric field-strength in the Lagrangian. We extend our procedure to the case of supersymmetric Ashtekar formalism in eight dimensions.Comment: 19 pages, Latex; section 6 improve

Impact of Multiple COVID-19 Waves on Gynaecological Cancer Services in the UK

Funding: This research was funded by the British Gynaecological Cancer Society (EMSG1L5R) and Ovacome charity. It is supported by the National Cancer Research Institute Gynaecological Cancer Clinical Studies Group and the British Association of Gynaecological Pathologists. The funding bodies had no role in the study design, data collection, analysis, interpretation or writing of the report, or decision to submit for publication. The research team was independent of funders. Acknowledgments: The study is supported by researchers at the Barts Cancer Research United Kingdom Centre for Excellence, Queen Mary University of London (C16420/A18066). We are grateful for the endorsement and support from charities and patient support groups such as Ovacome, The Eve Appeal, Target Ovarian Cancer, Ovarian Cancer Action, Jo’s Cervical Cancer Trust, and GO Girls. We are grateful for the support received from the Royal College of Obstetricians and Gynaecologists, the National Cancer Research Institute Gynaecological Cancer Clinical Studies Group, and the British Association of Gynaecological Pathologists.Peer reviewedPublisher PD

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes